Human breath contains a variety of volatile organic compounds (VOCs), also known as biomarkers. The concentration of specific biomarkers can be directly linked to a particular disease or health issue. One of the best known and well-studied biomarkers is acetone. Under normal circumstances, our body relies on glucose to provide energy. However, in the condition of glucose depletion, for example due to diet or exercise or having untreated diabetes, the body switches to fat-burning as source of energy and acetone is released into breath during this process. For healthy people with normal diet and activities, the typical breath acetone concentration is below 1 part per million (ppm). Elevated acetone concentration above 1 ppm is a sign for Type 1 or Type 2 diabetes or suggests burning of body fat.
Compared to other diagnosis methods, breath analysis is non-invasive, pain-free, cost effective and easily repeatable. Breath analysis is therefore a very powerful tool for clinical diagnosis or personal health monitoring.
Conventional breath analysis is conducted using gas chromatography with detection methods such as flame ionisation, ion mobility spectrometer and mass spectrometer. These instruments are expensive, bulky and require skilled operators, and thus can only be used in a lab. Other breath analyzers include optical sensors, semiconductor sensors and chemical sensors. Both semiconductor sensors and chemical sensors suffer from low sensitivity and absorption interferences from other VOCs present in both air and breath. Optical sensors can be based on absorption, fluorescence or photoacoustic effects. They are typically more specific and offer higher sensitivity.
The typical concentrations of VOCs in breath are very low, normally in the range of parts per billion (ppb) to ppm. For a breath analyzer based on optical absorption to detect such a small concentration, a long optical path length of the light through the breath is generally necessary. At the same time, it is preferable for a breath analyzer to be compact and portable. Therefore, a compact multipass absorption cell provides a good solution. Furthermore, as VOC concentration in different stages of a breath may vary (e.g. a variation between the start of exhalation and end of exhalation of a breath) and can sometimes provide important medical information, there is a need for a breath analyzer to be able to do real-time measurement.
Traditional multipass absorption cells, such as the Pfund cell, White cell, Herriot cell and circular multipass cell, work by using focusing mirrors to restrict the beam to a predefined space along a controlled path until the beam exits the cells. Since the beam must travel along a controlled path, these cells only work well with well collimated and narrow beam such as lasers.
U.S. Pat. No. 5,570,697A to Walker et al. (1996) describes a multipass cell based on light being reflected between multiple retroreflectors and/or prisms. Again, due to the requirement for controlled beam path, this cell only works for laser beams.
Long optical pathlengths can also be achieved from resonant cavity, such as in cavity ring-down spectroscopy (CRDS) and cavity enhanced absorption spectroscopy (CEAS). Examples include U.S. Pat. No. 8,399,837B2 (Robbins et al., published Mar. 19, 2013), US20040137637A1 (Wang et al., published Jul. 15, 2004), CN105259114A (Li, published Jan. 20, 2016), CN104251841A (Wang et al., published Dec. 31, 2014), and CN205157417U (Suzhou, published Apr. 13, 2016).
Patent Publication WO2015019650A1 to Shioni et al. (2013) describes a breath analyzer based on a double-pass absorption cell.
Patent Publication WO2011117572A1 to Hancock et al. (2010) teaches use of a broadband near infra-red (NIR) light source for breath acetone detection using a resonant optical cavity.
Patent Publication US20040137637A1 to Wang et al. (2003) teaches use of an ultraviolet (UV) light source for breath acetone detection using a resonant optical cavity.
Patent Publication US20160054294A1 to Rihani et al. (2014) presents a gas sensor using one or more UV light emitting diodes (LEDs), especially for measuring acetone in breath.
Use of flow straighteners (honeycombs) for generation of laminar flow is well known, for example in U.S. Pat. No. 8,421,979 to Josephus et al. (1995). The cross-section shapes of these “honeycombs” may be of square, circular and regular hexagonal cells.
U.S. Pat. No. 5,351,120A to Jurcik et al. (1993) presents a conically-shaped spectroscopic sample cell design to reduce gas vortices with the aim of purging the cell more efficiently for accurate measurement of trace impurities.
U.S. Pat. No. 8,194,249B2 to Haveri et al. (2009) proposes a gas cell design to maintain constant and laminar flow throughout and to reduce dead space during gas flow, thereby improving the response time of the analyzer.